In spite of antibiotics, pneumococcal disease is a major cause of infection in infants and in the elderly. In the United States it is still the leading cause of death by infectious agents. It is the major cause of otitis media, which accounts for most of the sick baby visits for pediatric care and meningitis caused by pneumococci is frequently fatal. The situation is particularly critical since the incidence of antibiotic resistant of pneumococci is increasing and since infants fail to make protective responses to the present pneumococcal vaccine. Our past studies indicate that antibodies in normal serum reactive with phosphocholine (PC), a species specific antigen of the pneumococcal cell wall, may play an important role in the "non-specific" immunity to pneumococcal infection. In the mouse, they provide a 1000-10,000-fold increase in resistance to infection with several strains of pneumococci. Although virtually all humans between the ages of 4 and 60 have circulating anti-PC antibody, infants and many elderly individuals lack detectable antibody. We propose to use epidemiological, in vitro, and mouse protection studies to determine if it is likely that human anti-PC antibodies contribute to the ability of humans to resist infection with pneumococci, and if a knowledge of serum anti-PC levels can help predict which individuals are susceptible to pneumococcal infection. We hope to make human monoclonal anti-PC antibodies, which should be very helpful in these investigations. We also plan to use mouse hybridoma anti-PC antibodies as a model system to compare the abilities of the different immunoglobulin isotypes to mediate various immunological processes. The T15 family of mouse anti-PC hybridoma antibodies will be important to those studies since they include antibodies of different isotypes that have virtually identical variable regions. These antibodies will be used to compare the abilities of antibodies of different isotypes to protect against pneumococcal infections in the blood, lung, middle ear, etc. and will allow us to compare the importance of Fc and C3b mediated opsonophaocytosis in the protection brought about by antibodies of different isotypes.